Efficient synthesis of chiral γ-aminobutyric esters via direct rhodium-catalysed enantioselective hydroaminomethylation of acrylates

Abstract

The first successful rhodium catalysed asymmetric hydroaminomethylation of alkenes using a single catalyst is reported with ees up to 86%.

Evolution in the metal-catalyzed asymmetric hydroformylation of 1,1′-disubstituted alkenes

“…For more sterically hindered alkenes (3-5) ligand with a (S)-σ-methylbenzyl amine substituent provided the best results. The results for substrates 5 and 9 are relevant since important biologically active molecules include a phenyl substituent in α-position and the catalysts reported to date (12,13,15) were only efficient for α-alkyl substituted substrates. Moreover, Rh/(S ax ,S ax )-L13 (R ¼ Cy) successfully promoted the onepot asymmetric HAM of different α-substituted acrylamides and amines to directly yield chiral γ-aminobutyric acid (GABA) derivatives, with also high yields and enantioselectivities (Scheme 10).…”

“…The success of (R,R)-BenzP* (L7) and (R,R)-QuinoxP* (L8) in the Rh-catalyzed AHF of acrylates (12), prompted Godard and co-workers to test them in the asymmetric intermolecular hydroaminomethylation (HAM) of α-alkyl acrylates (13). In this case, (R,R)-QuinoxP* (L8) showed the best catalytic performance.…”

Rh-Catalyzed Asymmetric Hydroaminomethylation of α-Substituted Acrylamides: Application in the Synthesis of RWAY

“…Finally, 2i bearing a phenyl group in the α-position and an azepanamide group was also obtained in good yield (52%) and high enantioselectivity (74%). The results for 2h and 2i are particularly relevant since important biologically active molecules include a phenyl substituent in α-position (Scheme ) and the catalysts reported to date ,, were only efficient for α-alkyl substituted substrates. The catalytic systems based on phosphite-phosphoramidite ligands L6 and L10 are thus efficient in the Rh-catalyzed asymmetric hydroformylation of α-substituted acrylamides (ee up to 99%), even for substrates with a phenyl group in α-position.…”

“…2 Recently, we reported the efficient Rh-catalyzed asymmetric HAM of α-alkyl acrylates to access chiral γ-aminobutyric esters using a single Rh-catalyst (Rh/(R,R-QuinoxP*) (Scheme 1B). 3 This work provided a straightforward access to chiral γaminobutyric acid (GABA) derivatives. 4,5 Among the GABA derivatives, those that contain an amide group are of paramount importance because this motif is present in CCR2 antagonists for chronic inflammatory processes such as atherosclerosis, multiple sclerosis, and rheumatoid arthritis 6 and CCR5 antagonists for HIV drug, 7a or for brain imaging.…”

“…In consequence, the efficiency and interest regarding the reaction are undermined . Recently, we reported the efficient Rh-catalyzed asymmetric HAM of α-alkyl acrylates to access chiral γ-aminobutyric esters using a single Rh-catalyst (Rh/( R , R -QuinoxP*) (Scheme B) . This work provided a straightforward access to chiral γ-aminobutyric acid (GABA) derivatives. , …”